Exploring TSLP and IL-33 Serum Levels and Genetic Variants: Unveiling Their Limited Potential as Biomarkers for Mild Asthma in Children.

As the burden of mild asthma is not well understood, the significance of expanding research in the group of patients with mild asthma is emphasized. Thymic stromal lymphopoietin (TSLP) and interleukin 33 (IL-33) are involved in the pathogenesis of atopy and the immune response to inhaled environmental insults, such as allergens, in asthmatic patients. Objectives: The objective of this study was to explore the correlation between specific polymorphisms within the genes encoding TSLP and IL-33, as well as the concentrations of TSLP and IL-33 in the serum, and the occurrence of pediatric mild asthma. Methods: The analysis encompassed 52 pediatric patients diagnosed with mild bronchial asthma, including both atopic and non-atopic cases, and a control group of 26 non-asthmatic children. Recruitment was conducted through a comprehensive questionnaire. Parameters such as allergic sensitization, serum levels of circulating TSLP and IL-33, and the identification of single-nucleotide polymorphisms in TSLP (rs11466750 and rs2289277) and IL-33 (rs992969 and rs1888909) were assessed for all participants. Results: Significantly lower mean serum TSLP concentrations were observed in asthmatic subjects compared to the control group, with atopic asthma patients showing even lower TSLP levels than non-atopic counterparts. No significant differences were found in mean serum IL-33 concentrations between the two groups. Considering the allele model, for both tested SNPs of IL-33, we observed that patients with asthma, atopic asthma, and atopy statistically less frequently possess the risk allele. Conclusions: Our study findings suggest that IL-33 and TSLP do not serve as ideal biomarkers for mild asthma in children. Their effectiveness as biomarkers might be more relevant for assessing disease severity rather than identifying asthma in pediatric patients. Further research focusing on the association between TSLP and IL-33 gene polymorphisms and asthma is expected to significantly advance disease management.

Peanut Allergy and Component-Resolved Diagnostics Possibilities-What Are the Benefits?

Peanut allergy is a widespread and potentially life-threatening condition that affects both children and adults, with a growing incidence worldwide. It is estimated to affect around 1-2% of the population in several developed countries. Component-resolved diagnostics is a modern approach to allergy diagnosis that focuses on identifying specific allergenic proteins to provide precise diagnoses and personalized treatment plans. It is a technique that enables the analysis of specific IgE antibodies against tightly defined molecules (components) that constitute the allergen. Component-resolved diagnostics is particularly valuable in peanut allergy diagnosis, helping to determine allergen components associated with severe reactions. It also aids in predicting the course of the allergy and enables the development of personalized immunotherapy plans; however, the full application of it for these purposes still requires more precise studies. In this paper, we present the current knowledge about peanut allergy and component-resolved diagnostics possibilities. We discuss the possibilities of using molecular diagnostics in the diagnosis of peanut allergy. We focus on examining and predicting the development of peanut allergy, including the risk of anaphylaxis, and describe the latest data related to desensitization to peanuts.

Dietary Polyphenols-Natural Bioactive Compounds with Potential for Preventing and Treating Some Allergic Conditions.

In light of the constantly increasing prevalence of allergic diseases, changes in dietary patterns have been suggested as a plausible environmental explanation for the development and progression of these diseases. Nowadays, much attention has been paid to the development of dietary interventions using natural substances with anti-allergy activities. In this respect, dietary polyphenols have been studied extensively as one of the most prominent natural bioactive compounds with well-documented anti-inflammatory, antioxidant, and immunomodulatory properties. This review aims to discuss the mechanisms underlying the potential anti-allergic actions of polyphenols related to their ability to reduce protein allergenicity, regulate immune response, and gut microbiome modification; however, these issues need to be elucidated in detail. This paper reviews the current evidence from experimental and clinical studies confirming that various polyphenols such as quercetin, curcumin, resveratrol, catechins, and many others could attenuate allergic inflammation, alleviate the symptoms of food allergy, asthma, and allergic rhinitis, and prevent the development of allergic immune response. Conclusively, dietary polyphenols are endowed with great anti-allergic potential and therefore could be used either for preventive approaches or therapeutic interventions in relation to allergic diseases. Limitations in studying and widespread use of polyphenols as well as future research directions are also discussed.

Exposure to farm environment and its correlations with total IgE, IL-13, and IL-33 serum levels in patients with atopy and asthma.

BACKGROUND: The aim of the study was to evaluate total immunoglobulin E (IgE), IL-13, and IL-33 serum level in people with bronchial asthma and atopy, and in healthy control group depending on their exposure to farm animals currently and in the first year of life. METHODS: The study included 174 individuals living in rural areas and in a small town. Standardized questions from the International Study of Asthma and Allergy in Childhood and The European Community Respiratory Health Survey (ECRHS) questionnaires were used to define asthma. Atopic status was verified by skin prick tests. Rural exposure including contact with livestock was verified by adequate questionnaire. Total serum IgE, IL-13, and IL-33 levels were assessed by ELISA (enzyme-linked immunosorbent assay) tests. RESULTS: Participants with atopy and bronchial asthma were characterized by high level of immunoglobulin E. Tendency to lower serum IgE level was observed among people reporting present contact with farm animals. Also, among those having contact with livestock in their first year of life, the analogous tendency was noticed. No difference in serum IL-13 levels in participants with asthma and atopy, and controls was observed, and there was no effect of exposure on farm animals on the concentration of IL-13. The highest IL-33 level was found in the atopic group, and the lowest in the control group. Participants currently exposed to farm animals were predisposed to have lower IL-33 serum level. CONCLUSION: Exposure of farm animals currently and in first year of life may result in a lower level of total IgE. Correlation between IL-13 and IL-33 serum levels and contact with livestock was not confirmed.

miRNAs as Modern Biomarkers in Asthma Therapy.

Asthma is a chronic inflammatory disease of the airways characterized by shortness of breath, chest tightness, coughing, and wheezing. For several decades (approximately 30 years), miRNAs and their role in asthma have been of constant interest among scientists. These small, non-coding RNA fragments, 18-25 nucleotides long, regulate gene expression at the post-transcriptional level by binding to the target mRNA. In this way, they affect several biological processes, e.g., shaping airway structures, producing cytokines and immune mediators, and controlling defense mechanisms. Publications confirm their potential role in the diagnosis and monitoring of the disease, but only some articles address the use of miRNAs in the treatment of asthma. The following paper reviews the latest available studies and presents miRNAs as a useful tool for predicting the effectiveness of the included treatment, early diagnosis of exacerbations, and in assessing patient compliance for different groups of drugs used in asthma. The latest known pathways underlying the pathogenesis of the disease, which are associated with a change in miRNA expression, may be precise targets of therapeutic activity in the future.

Bacterial Microbiota of Asthmatic Children and Preschool Wheezers' Airways-What Do We Know?

Asthma is the most chronic pulmonary disease in pediatric population, and its etiopathology still remains unclear. Both viruses and bacteria are suspected factors of disease development and are responsible for its exacerbation. Since the launch of The Human Microbiome Project, there has been an explosion of research on microbiota and its connection with various diseases. In our review, we have collected recent data about both upper- and lower-airway bacterial microbiota of asthmatic children. We have also included studies regarding preschool wheezers, since asthma diagnosis in children under 5 years of age remains challenging due to the lack of an objective tool. This paper indicates the need for further studies of microbiome and asthma, as in today's knowledge, there is no particular bacterium that discriminates the asthmatics from the healthy peers and can be used as a potential biological factor in the disease prevalence and treatment.

Epicutaneous Sensitization and Food Allergy: Preventive Strategies Targeting Skin Barrier Repair-Facts and Challenges.

Food allergy represents a growing public health and socio-economic problem with an increasing prevalence over the last two decades. Despite its substantial impact on the quality of life, current treatment options for food allergy are limited to strict allergen avoidance and emergency management, creating an urgent need for effective preventive strategies. Advances in the understanding of the food allergy pathogenesis allow to develop more precise approaches targeting specific pathophysiological pathways. Recently, the skin has become an important target for food allergy prevention strategies, as it has been hypothesized that allergen exposure through the impaired skin barrier might induce an immune response resulting in subsequent development of food allergy. This review aims to discuss current evidence supporting this complex interplay between the skin barrier dysfunction and food allergy by highlighting the crucial role of epicutaneous sensitization in the causality pathway leading to food allergen sensitization and progression to clinical food allergy. We also summarize recently studied prophylactic and therapeutic interventions targeting the skin barrier repair as an emerging food allergy prevention strategy and discuss current evidence controversies and future challenges. Further studies are needed before these promising strategies can be routinely implemented as prevention advice for the general population.

The Potential Role of Serum and Exhaled Breath Condensate miRNAs in Diagnosis and Predicting Exacerbations in Pediatric Asthma.

Asthma is the most common chronic disease of the respiratory system in children and the number of new cases is constantly increasing. It is characterized by dyspnea, wheezing, tightness in the chest, or coughing. Due to diagnostic difficulties, disease monitoring, and the selection of safe and effective drugs, it has been shown that among the youngest patients, miRNAs fulfilling the above roles can be successfully used in common clinical practice. These biomolecules, by regulating the expression of the body's genes, influence various biological processes underlying the pathogenesis of asthma, such as the inflammatory process, remodeling, and intensification of airway obstruction. They can be detected in blood serum and in exhaled breath condensate (EBC). Among children, common factors responsible for the onset or exacerbation of asthma, such as infections, allergens, air pollution, or tobacco smoke present in the home environment, cause a change the concentration of miRNAs in the body. This is related to their significant impact on the modulation of the disease process. In the following paper, we review the latest knowledge on miRNAs and their use, especially as diagnostic markers in assessing asthma exacerbation, with particular emphasis on the pediatric population.

Airway Bacterial Biodiversity in Exhaled Breath Condensates of Asthmatic Children-Does It Differ from the Healthy Ones?

Asthma etiopathology is still not fully determined. One of its possible causes can be found in airway microbiome dysbiosis. The study's purpose was to determine whether there are any significant differences in the bacterial microbiome diversity of lower airways microbiota of asthmatic children, since knowledge of this topic is very scarce. To the authors' knowledge, this is the first research using exhaled breath condensates in children's lower airways for bacterial assessment. Exhaled breath condensates (EBC) and oropharyngeal swabs were obtained from pediatric asthmatic patients and a healthy group (n = 38, 19 vs. 19). The microbial assessment was conducted through genetic material PCR amplification, followed by bacterial 16S rRNA amplicon sequencing. Collected data were analyzed, in terms of taxonomy and alpha and beta diversity between assessed groups. Swab samples are characterized by higher species richness compared to exhaled breath condensates (Shannon diversity index (mean 4.11 vs. 2.867, p = 9.108 × 10-8), observed features (mean 77.4 vs. 17.3, p = 5.572 × 10-11), and Faith's phylogenetic diversity (mean 7.686 vs. 3.280 p = 1.296 × 10-10)). Asthmatic children had a higher abundance of bacterial species (Shannon diversity index, mean 3.029 vs. 2.642, p = 0.026) but more even distribution (Pielou's evenness, mean 0.742 vs. 0.648, p = 0.002) in EBC than healthy ones; the same results were observed within pediatric patients born naturally within EBC samples. In children with a positive family history of allergic diseases, alpha diversity of lower airway material was increased (Shannon's diversity index p = 0.026, Faith's phylogenetic diversity p = 0.011, observed features p = 0.003). Class Gammaproteobacteria and Bacilli were less abundant among asthmatics in the exhaled breath samples. The most dominant bacteria on a phylum level in both sample types were Firmicutes, followed by Proteobacteria and Actinobacteriota. The obtained outcome of higher bacterial diversity of lower airways among asthmatic patients indicates a further need for future studies of microbiota connection with disease pathogenesis.

The Impact of Dietary Intervention in Obese Children on Asthma Prevention and Control.

The prevalence of both asthma and obesity in the pediatric population is steadily increasing, and even the obese-asthma phenotypes are postulated. Obese children with asthma experience more asthma symptoms, more frequent exacerbations, and worse response to treatment; they also report a lower quality of life compared with lean asthmatics. Some of the etiological factors for asthma and obesity may overlap. Perhaps asthma and obesity share a common genetic and immunologic origin. Diet is a compelling modifiable factor in obesity and asthma prevention and control, although the relationship between these two diseases is certainly multifactorial. In this article, we analyze the impact of dietary intervention and weight loss in obese children on asthma prevention and control.

Genetic Variants in Epidermal Differentiation Complex Genes as Predictive Biomarkers for Atopic Eczema, Allergic Sensitization, and Eczema-Associated Asthma in a 6-Year Follow-Up Case-Control Study in Children.

Atopic eczema is the most common chronic inflammatory skin disease of early childhood and is often the first manifestation of atopic march. Therefore, one challenge is to identify the risk factors associated with atopic eczema that may also be predictors of atopic disease progression. The aim of this study was to investigate the association of SNPs in hornerin (HRNR) and filaggrin-2 (FLG2) genes with childhood atopic eczema, as well as other atopic phenotypes. Genotyping for HRNR and FLG2 was performed in 188 children younger than 2 years of age, previously screened for the FLG null mutations, and followed at yearly intervals until the age of 6. We demonstrated that risk variants of HRNR rs877776[C] and FLG2 rs12568784[T] were associated with atopic eczema, allergic sensitization, and susceptibility to the complex phenotype-asthma plus eczema. These effects seem to be supplementary to the well-known associations for FLG mutations and may be modulated by gene-gene interactions. Additionally, in children with eczema, these genetic variants may also be considered, along with FLG mutations, as predictive biomarkers for eczema-associated asthma. In conclusion, our results indicate that genetic variants in the epidermal differentiation complex gene could contribute to the pathogenesis of atopic eczema and progression to subsequent allergic disease.

Fermented Food in Asthma and Respiratory Allergies-Chance or Failure?

In the last few decades, a dramatic increase in the global prevalence of allergic diseases and asthma was observed. It was hypothesized that diet may be an important immunomodulatory factor influencing susceptibility to allergic diseases. Fermented food, a natural source of living microorganisms and bioactive compounds, has been demonstrated to possess health-promoting potentials and seems to be a promising strategy to reduce the risk of various immune-related diseases, such as allergic diseases and asthma. The exact mechanisms by which allergic diseases and asthma can be alleviated or prevented by fermented food are not well understood; however, its potential to exert an effect through modulating the immune response and influencing the gut microbiota has been recently studied. In this review, we provide the current knowledge on the role of diet, including fermented foods, in preventing or treating allergic diseases and asthma.

Metabolites of L-ARG in Exhaled Breath Condensate and Serum Are Not Biomarkers of Bronchial Asthma in Children.

(1) Background: L-arginine (L-ARG) and its metabolites are involved in some aspects of asthma pathogenesis (airway inflammation, oxidative stress, bronchial responsiveness, collagen deposition). Published data indicate that lungs are a critical organ for the regulation of L-ARG metabolism and that alterations in L-ARG metabolism may be significant for asthma. The aim of this study was to assess the levels of L-ARG and its metabolites in pediatric patients with asthma in serum and exhaled breath condensate (EBC) by mass spectrometric analysis and compare them with non-asthmatic children. (2) Methods: Sixty-five children (37 pediatric patients with bronchial asthma and 28 healthy control subjects) aged 6-17 participated in the study. All participants underwent a clinical visit, lung tests, allergy tests with common aeroallergens, and serum and EBC collection. The levels of biomarkers were determined in both serum and EBC. Analytical chromatography was conducted using an Acquity UPLC system equipped with a cooled autosampler and an Acquity HSS T3 column. Mass spectrometric analysis was conducted using the Xevo G2 QTOF MS with electrospray ionization (ESI) in positive ion mode. (3) Results: Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels in serum and EBC did not differ significantly in asthmatic children and healthy control subjects. We found no correlation between forced expiratory volume in one second (FEV1) and L-ARG and its metabolites, as well as between interleukin-4 (IL-4) serum level and L-ARG and its metabolites. Concentrations of ADMA, SDMA, citrulline (CIT), and ornithine (ORN) were higher in serum than EBC in asthmatics and non-asthmatics. By contrast, concentrations of dimethylarginine (DMA) were higher in EBC than serum. ADMA/L-ARG, SDMA/L-ARG, and DMA/L-ARG ratios were significantly higher in EBC than in serum in asthmatics and in non-asthmatics. (4) Conclusions: Serum and EBC concentrations of L-ARG and its metabolites were not an indicator of pediatric bronchial asthma in our study.

Exhaled Breath Condensate-A Non-Invasive Approach for Diagnostic Methods in Asthma.

The pathophysiology of asthma has been intensively studied, but its underlying mechanisms such as airway inflammation, control of airway tone, and bronchial reactivity are still not completely explained. There is an urgent need to implement novel, non-invasive diagnostic tools that can help to investigate local airway inflammation and connect the molecular pathways with the broad spectrum of clinical manifestations of asthma. The new biomarkers of different asthma endotypes could be used to confirm diagnosis, predict asthma exacerbations, or evaluate treatment response. In this paper, we briefly describe the characteristics of exhaled breath condensate (EBC) that is considered to be an interesting source of biomarkers of lung disorders. We look at the composition of EBC, some aspects of the collection procedure, the proposed biomarkers for asthma, and its clinical implications. We also indicate the limitations of the method and potential strategies to standardize the procedure of EBC collection and analytical methods.

Primary Prevention of Food Allergy-Environmental Protection beyond Diet.

A food allergy is a potentially life-threatening disease with a genetic and environmental background. As its prevalence has increased significantly in recent years, the need for its effective prevention has been emphasized. The role of diet modifications and nutrients in food allergy reduction has been extensively studied. Much less is known about the role of other environmental factors, which can influence the incidence of this disease. Changes in neonates gut microbiome by delivery mode, animal contact, inhalant allergens, oral and then cutaneous allergen exposure, air pollution, smoking, infections and vaccinations can be the potential modifiers of food allergy development. There is some data about their role as the risk or preventive factors, but yet the results are not entirely consistent. In this paper we present the current knowledge about their possible role in primary prevention of food allergies. We discuss the mechanisms of action, difficulties in designing accurate studies about food allergy and the potential biases in interpreting the connection between environmental factors and food allergy prevention. A better understanding of the role of environmental factors in food allergies development may help in implementing practical solutions for food allergy primary prevention in the future.

Apple allergy: Causes and factors influencing fruits allergenic properties-Review.

BACKGROUND: Apple tree fruits (Malus × domestica Borkh.) are a rich source of nutrients and nutraceuticals and are recommended as a part of the healthy, staple diet. However, apples could be also the cause of allergies including severe reactions. Allergies to fruits like apples are predominantly associated with pollinosis. In North and Central Europe, sensitisation to apples is caused mainly by cross-reactive birch pollen aeroallergen, whereas in the Mediterranean area of Europe, apple allergy is mostly associated with allergies to peach. The allergenicity of apples differ across cultivars but only a few varieties were studied. Some factors changing apples allergenicity were identified, including unmodifiable and potentially modifiable factors for example cultivation method, ripening stage and storage conditions. AIM: This review presents current knowledge about the molecular basis of apple allergenicity and factors influencing its level. CONCLUSIONS: Selecting cultivars with low potential of allergenicity, removing apple peel and heat treatment could reduce the risk of severe allergy reaction incidence and presumably can be used in birch pollen immunotherapy.

Diet Modifications in Primary Prevention of Asthma. Where Do We Stand?

The steep increase in asthma prevalence, observed worldwide in recent decades, has created an urgent need to search for effective methods of its prevention. Among other environmental factors, changes in diet habits and the potential influence of individual food components on immunological processes have been extensively studied as a potential method of intervention in primary prevention of asthma. The preventive role of some nutrients has been confirmed: unpasteurized milk reduced the risk of asthma in epidemiological studies, vitamin D supplementation was effective in preventing the transient forms of wheezing in small children and high maternal intake of fish oil reduced the risk of persistent wheeze and asthma in children. However, not all studies provided consistent results, and many food ingredients are still pending for defining their role in asthma development. Moreover, a novel approach looking not only at single food ingredients, but the whole dietary patterns and diversity has recently been proposed. In this paper, we discuss the current role of nutrients in asthma primary prevention and the reasons for inconsistencies in the study results. We look at single diet components, but also the whole dietary patterns. We describe the proposed mechanisms of action at different stages of life, identify the role of modifiers and delineate future perspectives on the application of nutrients in targeting strategies for asthma primary prevention.

The Role of Vitamin D in Respiratory Allergies Prevention. Why the Effect Is so Difficult to Disentangle?

Asthma and allergic rhinitis are the most common chronic childhood diseases with an increasing prevalence worldwide. There is an urgent need to look for methods of preventing allergic diseases from an early age. The relationship between vitamin D status and allergic diseases has been discussed in several studies recently. 25-hydroxyvitamin D (25(OH)D) is suggested to affect the development and/or severity of asthma and allergic rhinitis. Observational studies have seemed to confirm that vitamin D deficiency may contribute to an increase in allergy and asthma. Following interventional studies, however, have yielded ambiguous results. In this review, we describe recent findings regarding 25(OH)D impact on allergic diseases and provide a systematic analysis of the causes of great variability of the achieved results in different studies.

Quality of life in allergic rhinitis - children's and their parents' perspective in polish urban and rural population.

BACKGROUND: Allergic rhinitis is a common chronic condition in the paediatric population. No reports regarding the quality of life in children with allergic rhinitis in the Polish population have been found in the available literature. The aim of this study was to assess and compare the quality of life in patients with allergic rhinitis reported by children and their parents living in a city and in rural areas, and to evaluate the possible relationships between the quality of life and the severity of symptoms. METHODS: Two hundred and eight children with allergic rhinitis participated in the study (89 girls, aged 6-17, mean age 11.7 ± 3). Children were asked to evaluate their rhinitis symptoms by using two scales: the Total 4 Symptom Score and the Visual Analogue Scale. The quality of life assessment included the KINDL-R questionnaire. RESULTS: Both for the T4SS and the VAS scale the severity of symptoms in children with seasonal rhinitis was significantly higher than in children allergic to perennial allergens. The quality of life total scores on the KINDL questionnaire was 45.6 ± 8.5 for the children and 73.7 ± 10.7 for the parents. In all the domains, except for physical health, the child's quality of life was rated significantly higher by parents than by children. The biggest discrepancy occurred in the domains: social contacts and family. CONCLUSIONS: Allergic rhinitis can disrupt the quality of life. Parents tend to overestimate their children's quality of life comparing to the children's own assessment. The quality of life in children with allergic rhinitis correlated with the severity of the clinical symptoms of the disease. Evaluation of the quality of life in children is an essential issue in clinical investigation of patients with allergic rhinitis. It is of great importance to ask children themselves about their quality of life than rely only on parental opinion.

Raw Cow's Milk and Its Protective Effect on Allergies and Asthma.

Living on a farm and having contact with rural exposures have been proposed as one of the most promising ways to be protected against allergy and asthma development. There is a significant body of epidemiological evidence that consumption of raw milk in childhood and adulthood in farm but also nonfarm populations can be one of the most effective protective factors. The observation is even more intriguing when considering the fact that milk is one of the most common food allergens in childhood. The exact mechanisms underlying this association are still not well understood, but the role of raw milk ingredients such as proteins, fat and fatty acids, and bacterial components has been recently studied and its influence on the immune function has been documented. In this review, we present the current understanding of the protective effect of raw milk on allergies and asthma.